1,2,4-trimethoxybenzene exerts multi-target effects against ulcerative colitis by inhibiting the NLRP3 inflammasome and remodeling the gut microbiota-metabolism axis.

Butyrate improves dextran sulfate sodium-induced enterotoxicity in broilers.

An algorithm-enhanced stool DNA system improves the differential diagnosis of colorectal cancer versus Crohn's disease in high-risk symptomatic patients.

Berberine pretreatment enhances the homing and anti-inflammatory efficacy of dental pulp mesenchymal stem cells in TNBS-induced inflammatory bowel disease via activating the CXCR4/SDF-1 signaling pathway.

Macrophage USP9X attenuates colitis by restricting oncostatin M production via K27-linked deubiquitination of STAT1.

Inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, are chronic, relapsing inflammatory disorders increasingly recognized as systemic conditions with significant extraintestinal manifestations. Over the past 3 decades, the prevalence of IBD has risen in parallel with obesity and related metabolic disorders, including type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), chronic kidney disease (CKD), metabolic dysfunction-associated steatotic liver disease (MASLD), and dyslipidemia. This parallel rise raises the possibility of shared or interacting biological pathways linking metabolic dysfunction and intestinal inflammation. Epidemiologic studies suggest increased risks of metabolic comorbidities in IBD independent of traditional factors, while mechanistic insights implicate systemic meta-inflammation, mesenteric adipose tissue remodeling (creeping fat), gut barrier dysfunction, and altered lipid and glucose metabolism. These pathways perpetuate a cycle of immune dysregulation and metabolic injury, amplifying disease severity and complications. Obesity and insulin resistance further impact IBD outcomes by altering pharmacokinetics and therapeutic response to biologics, with a higher body mass index associated with increased treatment failure, earlier loss of response, and heightened infection risk. Emerging data also suggest potential dual benefits of metabolic-directed therapies, such as glucagon-like peptide-1 receptor agonists, which may improve weight, glycemic control, and inflammatory indices. However, most evidence remains observational, with limited longitudinal or mechanistic studies. This narrative review synthesizes current knowledge at the interface of IBD and metabolic dysfunction, highlighting clinical implications, translational insights, and research gaps. Integrating metabolic screening and multidisciplinary management into IBD care may improve outcomes, while future mechanistic and interventional studies are needed to define therapeutic strategies that address both gut inflammation and systemic metabolic disease.

Pathological reprogramming of innate immune cells drives resistance to biologics in inflammatory bowel diseases.

Fatty acid oxidation and inflammatory bowel disease: Highlighting the roles of pathogenesis and treatment.

Dual benefits of Xiao Chai Hu Tang and its active compounds in CPT-11 therapy: intestinal protection via barrier restoration and anti-inflammation combined with enhanced tumor apoptosis.

Dietary fiber (DF) in poultry nutrition was once viewed mainly as an anti-nutritional factor that reduced energy density and nutrient digestibility. Current research shows DF can play important functional roles in gut health, nutrient utilization, and overall performance when its type and inclusion level are carefully managed. Fiber fractions differ widely in chemical composition and physical properties such as solubility, water-holding capacity, and water-binding capacity. These factors influence digesta viscosity, passage rate, microbial fermentation, and satiety, making precise fiber characterization critical for effective diet formulation. Traditional methods like crude fiber analysis underestimate total fiber and miss key soluble fractions. Modern approaches, including total dietary fiber analysis and near-infrared spectroscopy allow for better quantification of both insoluble and soluble components and support incorporation into real-time feed formulation. By understanding and targeting specific non-starch polysaccharides or oligosaccharides, nutritionists can promote beneficial fermentation, encourage short-chain fatty acid (SCFA) production, and minimize undesirable protein fermentation or pathogen growth. Dietary fiber also supports intestinal barrier function by stimulating gut development, increasing villus height, and fueling epithelial cells through SCFAs. However, poorly balanced fiber can impair nutrient absorption, increase maintenance energy needs, or elevate digesta viscosity, particularly in young birds. Monitoring gut health is now possible by using biomarkers as tools to evaluate intestinal integrity, inflammation, and microbial balance as we investigate the impact of dietary fiber, but further work is needed to standardize these measures and account for flock variability When properly applied, DF can enhance feed efficiency, improve welfare by reducing hunger-driven behaviors, support reproductive performance, and strengthen disease resilience. A data-driven, precision approach combining accurate fiber analysis, enzyme supplementation, microbiome profiling, and non-invasive gut health biomarkers offers the greatest potential to optimize both productivity and sustainability in poultry systems. The purpose of this symposium was to stimulate discussion and enhance understanding of dietary fiber and its potential benefits in improving poultry production. This paper provides an overview of each contributing author's role in the symposium. Dr. Caitlin Evans addressed the challenges associated with current fiber nomenclature and emphasized the need to improve analytical methods and overall understanding of fiber. She brings strong credibility to this topic as a Technical Manager for Near-Infrared Spectroscopy and Feed Milling Engineer at AB Vista, and as a Ph.D. graduate of Kansas State University. Dr. Amy Petry shared her expertise on the impact of fiber in swine nutrition and how these findings can be applied to poultry. She is an Assistant Professor in the Division of Animal Sciences at the University of Missouri, where her research focuses on improving fiber utilization and its effects on energy efficiency and animal health. Dr. Tim Johnson, Professor in the Department of Veterinary and Biomedical Sciences at the University of Minnesota, highlighted the importance of understanding the poultry microbiome and its role in developing strategies to enhance bird performance. Dr. Mike Kogut contributed his expertise as a Research Microbiologist and Lead Scientist with the Food and Feed Safety Research Unit at the Southern Plains Agricultural Research Center. Finally, Dr. Carrie Walk, Head of Research at AB Vista, along with Dr. Tara York, AB Vista's Technical Director for North America, integrated the key themes of the symposium, connecting the presented research and practical applications.

Dysfunctional intestinal fibrosis is an irreversible complication of Crohn's disease (CD). The complex heterogeneity of intestinal mesenchymal cells makes it difficult to understand the pathogenesis of intestinal fibrosis. Previously, we identified Meflin as a marker of fibroblast subsets. This study aimed to explore the role of Meflin-positive fibroblasts in intestinal fibrogenesis and investigate the potential of pharmacological control of Meflin expression as a treatment for patients with CD. Our results indicated that Meflin expression was upregulated in fibroblasts at the early stage of fibrosis but was downregulated in established fibrosis in both patients with CD and 2 different mouse models, which are the chronic dextran sodium sulfate (DSS) model and an IL-10-deficient model that spontaneously develops intestinal inflammation. Meflin-deficient mice exacerbated intestinal fibrosis with dysregulated expression of noncanonical Wnt ligand WNT5A and its receptor ROR2. Pharmacologically induced Meflin expression through the administration of a synthetic retinoid reversed intestinal fibrosis in the DSS model and suppressed profibrotic protein secretion in fibroblasts isolated from patients with CD. Our findings indicate that Meflin-positive fibroblasts represent a functional subpopulation that suppresses intestinal fibrosis. Augmentation of Meflin expression shows antifibrotic effects and holds promise as a therapeutic approach for intestinal fibrosis in patients with CD.

Diet impacts the pathogenesis of gastrointestinal diseases including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Although dietary protein can influence physiologic health, its impact on these diseases has not been adequately investigated. Consequently, clinical guidelines on optimal protein intake (i.e. amount and source) to help prevent or treat these conditions are limited. Recent preclinical and clinical studies have examined how modifying dietary protein can impact the pathogenesis of intestinal inflammation. For example, work in mice reveals that higher protein intake worsens colitis and that different dietary protein sources can exert differential effects on colitis severity. Microbial populations and their metabolism were shown to play an important role in mediating these effects. Studies in humans have shown that high intake of red meat is associated with increased IBD incidence and decreased time to relapse in patients with ulcerative colitis; however, it is unclear which other protein sources may be more beneficial. Although a direct connection between dietary protein and CRC has not been established, multiple preclinical studies have shown that reducing dietary protein exerts anticancer effects, including improved response to therapy across multiple tumor types. These effects were shown to be predominantly mediated by restricting tumors of exogenous growth-promoting amino acids, resulting in tumor stress, and in certain cases, activation of antitumor immunity. As a result of multiple studies, we have gained important insights into the role of dietary protein in mediating colonic inflammation and cancer. This work motivates clinical studies to directly test whether modifying source or amount of protein intake in patients with IBD or CRC will be beneficial for reducing disease severity and improving response to therapy.

Dangshen formula Shengmai-Yin suppresses atherosclerosis through restoring the gut microbiota and homeostatic efferocytosis.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic disorder that markedly impairs quality of life. Current diagnostic and monitoring tools rely on invasive procedures such as endoscopy, which are costly and burdensome. Volatile organic compounds (VOCs) in breath and feces, reflecting host-microbiota metabolism, have emerged as promising non-invasive biomarkers, but their clinical utility remains underexplored.This study aimed to identify breath- and feces-derived VOCs as novel biomarkers for IBD and to establish artificial intelligence (AI)-based predictive models for non-invasive diagnosis and disease activity monitoring. The relationship between VOC alterations and gut microbiota dysbiosis was also investigated. A total of 279 participants (131 IBD patients, 148 healthy controls) were enrolled. VOCs from breath and fecal samples were analyzed using gas chromatography-ion mobility spectrometry (GC-IMS). AI-based machine learning models were developed for diagnosis and monitoring. Furthermore, the differences in breath VOCs identified in human cohorts were validated in a DSS-induced colitis mouse model (2% DSS for 7 days). In a subset of 62 individuals, 16S rDNA sequencing characterized gut microbiota composition and its correlation with VOCs. Distinct VOC profiles were identified in IBD. Ethyl sulfide and furfural were elevated in breath samples, while hexanoic acid, pentanoic acid, thiophene, and ethyl acetate were reduced. In fecal samples, dimethyl trisulfide increased, whereas several short-chain fatty acids(SCFAs) and alcohols decreased. The diagnostic model achieved an AUC of 0.92 (sensitivity 96%, specificity 71%), and the monitoring model an AUC of 0.88, both outperforming C-reactive protein and fecal calprotectin. Validation in a DSS-induced colitis model confirmed eight discriminatory VOCs, characterized by depleted SCFA-related VOCs and elevated sulfide VOCs, underscoring their robust correlation with the development and severity of intestinal inflammation. IBD patients showed reduced microbial diversity and depletion of short-chain fatty acid-producing bacteria, closely correlated with altered VOC profiles. This study demonstrates that integrating volatomics with AI-based modeling enables accurate, non-invasive diagnosis and monitoring of IBD. The cross-species consistency observed in our human cohorts and DSS-induced colitis mice confirms the reliability of specific VOCs as conserved inflammatory biomarkers. These findings, coupled with VOC-microbiota associations, offer profound mechanistic insights and a promising platform for biomarker-guided precision care. ChiCTR, ChiCTR2300073475. Registered 12 July 2023-Prospectively registered, https://www.chictr.org.cn/bin/project/edit?pid=201603 .

The complement system is one of the most evolutionarily conserved arms of innate immunity and has re-emerged as an important regulator of intestinal inflammation in inflammatory bowel disease (IBD). Early observations from the mid-1970 s such as complement deposition in diseased bowel tissue and elevated serum complement levels in patients with ulcerative colitis and Crohn's disease have evolved into a nuanced understanding of how individual complement components can exert both protective and pathogenic effects in IBD. This review highlights recent advances in complement biology and examines how complement shapes intestinal immune responses, particularly in the setting of ongoing inflammation. The complement system consists of more than 60 proteins that act as rapid first responders to infection. Although traditionally considered primarily liver-derived circulating effectors, recent work has demonstrated local synthesis and activation of key complement components at mucosal sites, including the colon. In parallel, genome-wide association studies have identified variants in complement genes associated with severe IBD complications. Collectively, these findings reveal a dichotomous role for complement in IBD, whereby excessive activation promotes inflammation, while impaired function compromises host defense and worsens disease outcomes. Complement-targeted therapies have been effective in other diseases but have not yet translated to IBD. A deeper understanding of context-dependent protective versus pathogenic complement functions will be essential for developing future therapeutic strategies.

Chen's Jinshui Pills ameliorate diabetic retinopathy in mice and are associated with intestinal barrier protection and anti-inflammatory effects.

Emamectin benzoate (EMB) is a novel and highly efficient insecticide. In the present study, we investigated the protective role of puerarin (PR) on EMB-induced intestinal injury in grass carp. Intestinal pathological damage was detected by H&E staining. Inflammatory cytokines were measured by qRT-PCR. Nrf2 signaling pathway was tested by western blot analysis. The results showed that EMB caused pathological damage to carp intestinal tissue, and PR could alleviate EMB-induced intestinal injury. PR significantly inhibited EMB-induced TNF-α, IL-1β, and IL-6 expression, as well as NF-κB activation in intestinal tissue. Furthermore, PR suppressed EMB-induced MDA and iron production and increased the production of GSH and CAT production, and GPX4 expression induced by EMB. Western blot results demonstrated that PR markedly increased the expression of Nrf2 and HO-1 in intestinal tissue. In conclusion, the results indicate that PR alleviates EMB-induced intestinal inflammation and ferroptosis in grass carp through activating Nrf2 signaling pathway. • Puerarin alleviated emamectin benzoate-induced TNF-α, IL-1β, and IL-6 production and NF-κB activation. • Puerarin alleviated emamectin benzoate-induced ferroptosis. • Nrf2 and HO-1 expression was increased by puerarin.

The potential of Bifidobacterium longum subsp. infantis in ameliorating traumatic brain injury-induced cognitive impairment in mice.

Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation and is thought to result from interactions among the immune system, environmental factors, and the gut microbiota in genetically susceptible individuals. Akkermansia muciniphila, a commensal bacterium has been reported to be depleted in individuals with IBD, although its precise role in intestinal inflammation remains unclear. This study examined the effects of A. muciniphila across multiple models of colitis, including dextran sulphate sodium (DSS)-induced colitis, the Mucin-2 knockout (Muc2-/-) model of spontaneous colitis, and Trichuris muris-mediated infectious colitis. In a DSS recovery model, treatment with pasteurized A. muciniphila reduced the severity of inflammation. However, when administered prior to DSS exposure, both live and pasteurized bacteria did not significantly reduce inflammatory markers, suggesting limited preventive effects. In T. muris-infected mice, supplementation with live A. muciniphila increased Th2 and anti-inflammatory cytokine responses, reduced parasite burden, and enhanced gene expression of the mucin Muc5ac. Additionally, both live and pasteurized A. muciniphila alleviated spontaneous colitis severity in Muc2-/- mice, indicating that these protective effects occur independently of Muc2. These findings expand understanding of the role of A. muciniphila in intestinal inflammation and highlight its potential as a therapeutic target for inflammatory intestinal disorders such as IBD.

Despite advances in therapy for inflammatory bowel disease (IBD), current treatments are associated with poor clinical outcomes and systemic side effects. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have therapeutic potential in IBD due to their regenerative and immunomodulatory properties. However, most studies administer MSC-EVs by injection, which does not offer the significant benefits of oral administration, including direct and localized access to the site(s) of intestinal inflammation. Here, we evaluated the stability of MSC-EVs for oral delivery by assessing particle size, concentration, and EV markers. MSC-EVs disintegrated in gastrointestinal (GI) fluids, with cryogenic electron microscopy confirming the loss of structural integrity. To address this, we developed a double-coating formulation consisting of chitosan and Eudragit S100 to enhance GI stability and facilitate colon-targeted delivery. Coated EVs were resistant to GI fluids and digestive enzymes, and the formulation released structurally intact, biologically active vesicles in colonic fluid. Preliminary in vivo studies showed that orally administered coated EVs reduced disease severity in a colitis mouse model and elicited a stronger therapeutic response than uncoated EVs administered orally or intravenously at the same dose. These findings indicate that, with appropriate formulation, oral delivery of MSC-EVs could be an effective route of administration to treat intestinal inflammation.